April Rose
Investigator, Lady Davis Institute
Assistant Professor, Department of Oncology, McGill University
Medical Oncologist, Segal Cancer Centre, Jewish General Hospital
Dr. April Rose is a clinician scientist and Assistant Professor within the Department of Oncology at McGill University. She is a staff Medical Oncologist at the Segal Cancer Centre of the Jewish General Hospital (CIUSSS West-Central Montreal) and a Principal Investigator at the Lady Davis Institute for Medical Research. Dr. Rose has clinical interests in melanoma and genitourinary cancers. Her research interests are in molecular and translational oncology as well as in the development of novel immunogenomic therapies for treatment resistant cancers.
Dr. Rose completed her Ph.D. in Experimental Medicine at McGill University under the supervision of Dr. Peter Siegel. During her Ph.D. she identified a novel protein, GPNMB and showed - using experimental models – that GPNMB is an important mediator of breast cancer metastasis. This work led to the clinical development of GPNMB targeted therapies for cancer patients.
During her medical training, Dr. Rose pursued postdoctoral research in melanoma translational biology, with a special focus on optimizing treatments for BRAF driven cancers. She and her team found that tumors with certain types of nonV600 BRAF mutation may be amenable to therapeutic intervention with clinically approved targeted therapies. While pursuing medical oncology residency at the University of Toronto and fellowship at the Princess Margaret Cancer Centre, Dr. Rose and her colleagues developed the BEAVER trial (NCT03839342) which is an investigator initiated clinical trial testing the efficacy of specific BRAF + MEK inhibitors in cancer patients with non-V600 BRAF mutations. This trial is actively enrolling and includes a number of correlative endpoints, which will allow the identification molecular mechanisms of therapeutic resistance.
Major Research Activities
1) Evaluating molecular mechanisms of therapeutic resistance in tumors with MAPK pathway mutations
Genes within the Mitogen Activated Protein Kinase (MAPK) pathway are frequently mutated driver oncogenes in cancer. Emerging targeted therapies for subsets of BRAF and RAS mutated cancers have had profound clinical impacts on cancer patient survival and quality of life. However, even with the most state-of-the-art precision therapies, duration of response is usually measured in months. We use highly robust pre-clinical in vitro and in vivo mouse models of NRAS and nonV600 BRAF mutated cancers to investigate the molecular mechanisms of therapeutic response and resistance. The goal of this research is to identify and test more effective treatments, which can be translated back into clinical trials for patients.
2) Assessing the impact of the metastatic bone tumor microenvironment on anti-cancer therapeutic responsiveness
Cancer patients with bone metastases experience high morbidity and mortality. Certain systemic therapies are less effective in cancer patients with bone metastases. The impact of the metastatic bone tumor microenvironment on responsiveness to targeted and immunotherapies is not well understood in bladder cancer and melanoma. We are employing syngeneic mouse models to investigate the impact of bone metastases on therapeutic responsiveness in these cancer types.
3) Minimally Invasive Precision Medicine for patients with Metastatic Cancer
Liquid biopsies are emerging and rapidly evolving group of medical technologies that can be used to assess risk of cancer recurrence and monitor response to treatment. I am interested in the development, evaluation and clinical implementation of liquid biopsies employing novel oncologic biomarkers. This research will assess the dynamic molecular evolution of tumors in cancer patients receiving precision therapies in order to facilitate real time therapeutic adaptation to ultimately improve patient outcomes.
Recent Publications
Rose AAN, Armstrong SM, Hogg D, Butler MO, Saibil SD, Arteaga DP, Pimentel Muniz T, Kelly D, Ghazarian D, King I, Kamil ZS, Ross K, Spreafico A.J. Biologic subtypes of melanoma predict survival benefit of combination anti-PD1+anti-CTLA4 immune checkpoint inhibitors versus anti-PD1 monotherapy. J Immunother Cancer. 2021 Jan;9(1):e001642. doi: 10.1136/jitc-2020-001642.PMID: 33483342
Dankner M, Lajoie M, Moldoveanu D, Nguyen TT, Savage P, Rajkumar S, Huang X, Lvova M, Protopopov A, Vuzman D, Hogg D, Park M, Guiot MC, Petrecca K, Mihalcioiu C, Watson IR, Siegel PM, Rose AAN. Dual MAPK Inhibition Is an Effective Therapeutic Strategy for a Subset of Class II BRAF Mutant Melanomas. Clin Cancer Res. 2018 Dec 15;24(24):6483-6494. doi: 10.1158/1078-0432.CCR-17-3384. Epub 2018 Jun 14PMID: 29903896
Rose AA, Annis MG, Frederick DT, Biondini M, Dong Z, Kwong L, Chin L, Keler T, Hawthorne T, Watson IR, Flaherty KT, Siegel PM. MAPK Pathway Inhibitors Sensitize BRAF-Mutant Melanoma to an Antibody-Drug Conjugate Targeting GPNMB. Clin Cancer Res. 2016 Dec 15;22(24):6088-6098. doi: 10.1158/1078-0432.CCR-16-1192. Epub 2016 Aug 11.PMID: 27515299
Dankner M, Rose AAN, Rajkumar S, Siegel PM, Watson IR. Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations. Oncogene. 2018 Jun;37(24):3183-3199. doi: 10.1038/s41388-018-0171-x. Epub 2018 Mar 15. PMID: 29540830